11-89007211-A-G

Variant names:

• chr11-89007211-A-G
• rs7120151
• NM_001143831.3:c.661+40001T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001143831.3(GRM5):​c.661+40001T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 152,154 control chromosomes in the GnomAD database, including 48,564 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.79 (48564 hom., cov: 33)
• Consequence: GRM5 NM_001143831.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.953
• Publications: 11 publications found

Genes affected

GRM5 (HGNC:4597): (glutamate metabotropic receptor 5) This gene encodes a member of the G-protein coupled receptor 3 protein family. The encoded protein is a metabatropic glutamate receptor, whose signaling activates a phosphatidylinositol-calcium second messenger system. This protein may be involved in the regulation of neural network activity and synaptic plasticity. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. A pseudogene of this gene has been defined on chromosome 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRM5	NM_001143831.3	c.661+40001T>C		intron_variant	Intron 2 of 9	ENST00000305447.5	NP_001137303.1
GRM5	NM_000842.5	c.661+40001T>C		intron_variant	Intron 2 of 8		NP_000833.1
GRM5	NM_001384268.1	c.661+40001T>C		intron_variant	Intron 2 of 8		NP_001371197.1
GRM5	XM_011542792.2	c.661+40001T>C		intron_variant	Intron 2 of 9		XP_011541094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRM5	ENST00000305447.5	c.661+40001T>C		intron_variant	Intron 2 of 9	1	NM_001143831.3	ENSP00000306138.4

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120418 AN: 152036 Hom.: 48500 Cov.: 33

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.887

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.788

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.792 AC: 120538 AN: 152154 Hom.: 48564 Cov.: 33 AF XY: 0.793 AC XY: 58950 AN XY: 74378

African (AFR) AF: 0.947 AC: 39340 AN: 41524

American (AMR) AF: 0.784 AC: 11994 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.706 AC: 2451 AN: 3472

East Asian (EAS) AF: 0.727 AC: 3759 AN: 5174

South Asian (SAS) AF: 0.887 AC: 4277 AN: 4824

European-Finnish (FIN) AF: 0.699 AC: 7375 AN: 10558

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.716 AC: 48662 AN: 67980

Other (OTH) AF: 0.790 AC: 1671 AN: 2114

Alfa AF: 0.739 Hom.: 62129

Bravo AF: 0.802

Asia WGS AF: 0.844 AC: 2937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.54
DANN	Benign	0.44
PhyloP100		-0.95
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7120151; hg19: chr11-88740379;